Injury severity and cell death mechanisms: Effects of concomitant hypovolemic hypotension on spinal cord ischemia-reperfusion in rats

Kang Lu, Cheng Loong Liang, Han Jung Chen, Shang Der Chen, Huan Chen Hsu, Po Chou Liliang, Tsu Kung Lin, Chung Lung Cho*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

38 Scopus citations

Abstract

A number of previous studies indicated that ischemia-reperfusion injury causes two distinct types of cell death - necrosis and apoptosis - in the central nervous system. It was also implicated that the intensity of injury can somehow affect the cell death mechanisms. By occluding the descending thoracic aorta with or without simultaneously induced hypovolemic hypotension in rats, we established a model of experimental spinal cord ischemia-reperfusion (I/R) in which the injury severity can be controlled. Recordings of carotid blood pressure (CBP) and spinal cord blood flow (SCBF) showed that aortic occlusion induced dramatic CBP elevation but SCBF drop in both the normotensive (NT) and hypotensive (HT) groups of rats. However, the HT group demonstrated significantly lower SCBF during aortic occlusion, and much slower elevation of SCBF after reperfusion, and extremely poor neurological performance. Spinal cord lesions were characterized by infarction associated with extensive necrotic cell death, but little apoptosis and caspase-3 activity. In contrast, in the NT group, I/R injury resulted in minor tissue destruction associated with persistent abundant apoptosis, augmented caspase-3 activity, and favorable functional outcome. The relative sparing of motoneurons in the ventral horns from apoptosis might have accounted for the minor functional impairment in the NT group. The severity of I/R injury was found to have substantial impact on the histopathological changes and cell death mechanisms, which correlate with neurological performance. Our results implicate that injury severity and duration after injury are two critical factors to be considered in therapeutic intervention.

Original languageEnglish
Pages (from-to)120-132
Number of pages13
JournalExperimental Neurology
Volume185
Issue number1
DOIs
StatePublished - 01 2004
Externally publishedYes

Keywords

  • Aortic occlusion
  • Apoptosis
  • Caspase-3
  • Hypotension
  • Hypovolemia
  • Ischemia-reperfusion
  • Necrosis
  • Spinal cord
  • Spinal cord blood flow

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